Liang Zhan

Jun Yu, Zhaoming Kong, Liang Zhan et al.

The assessment of Alzheimer's Disease (AD) and Mild Cognitive Impairment (MCI) associated with brain changes remains a challenging task. Recent studies have demonstrated that combination of multi-modality imaging techniques can better reflect pathological characteristics and contribute to more accurate diagnosis of AD and MCI. In this paper, we propose a novel tensor-based multi-modality feature selection and regression method for diagnosis and biomarker identification of AD and MCI from normal controls. Specifically, we leverage the tensor structure to exploit high-level correlation information inherent in the multi-modality data, and investigate tensor-level sparsity in the multilinear regression model. We present the practical advantages of our method for the analysis of ADNI data using three imaging modalities (VBM- MRI, FDG-PET and AV45-PET) with clinical parameters of disease severity and cognitive scores. The experimental results demonstrate the superior performance of our proposed method against the state-of-the-art for the disease diagnosis and the identification of disease-specific regions and modality-related differences. The code for this work is publicly available at https://github.com/junfish/BIOS22.

Hejie Cui, Wei Dai, Yanqiao Zhu et al.

Mapping the connectome of the human brain using structural or functional connectivity has become one of the most pervasive paradigms for neuroimaging analysis. Recently, Graph Neural Networks (GNNs) motivated from geometric deep learning have attracted broad interest due to their established power for modeling complex networked data. Despite their superior performance in many fields, there has not yet been a systematic study of how to design effective GNNs for brain network analysis. To bridge this gap, we present BrainGB, a benchmark for brain network analysis with GNNs. BrainGB standardizes the process by (1) summarizing brain network construction pipelines for both functional and structural neuroimaging modalities and (2) modularizing the implementation of GNN designs. We conduct extensive experiments on datasets across cohorts and modalities and recommend a set of general recipes for effective GNN designs on brain networks. To support open and reproducible research on GNN-based brain network analysis, we host the BrainGB website at https://braingb.us with models, tutorials, examples, as well as an out-of-box Python package. We hope that this work will provide useful empirical evidence and offer insights for future research in this novel and promising direction.

Carlo Amodeo, Igor Fortel, Olusola Ajilore et al.

Graph theoretical analyses have become standard tools in modeling functional and anatomical connectivity in the brain. With the advent of connectomics, the primary graphs or networks of interest are structural connectome (derived from DTI tractography) and functional connectome (derived from resting-state fMRI). However, most published connectome studies have focused on either structural or functional connectome, yet complementary information between them, when available in the same dataset, can be jointly leveraged to improve our understanding of the brain. To this end, we propose a function-constrained structural graph variational autoencoder (FCS-GVAE) capable of incorporating information from both functional and structural connectome in an unsupervised fashion. This leads to a joint low-dimensional embedding that establishes a unified spatial coordinate system for comparing across different subjects. We evaluate our approach using the publicly available OASIS-3 Alzheimer's disease (AD) dataset and show that a variational formulation is necessary to optimally encode functional brain dynamics. Further, the proposed joint embedding approach can more accurately distinguish different patient sub-populations than approaches that do not use complementary connectome information.

Haoteng Tang, Xiyao Fu, Lei Guo et al.

MRI-based modeling of brain networks has been widely used to understand functional and structural interactions and connections among brain regions, and factors that affect them, such as brain development and disease. Graph mining on brain networks may facilitate the discovery of novel biomarkers for clinical phenotypes and neurodegenerative diseases. Since brain networks derived from functional and structural MRI describe the brain topology from different perspectives, exploring a representation that combines these cross-modality brain networks is non-trivial. Most current studies aim to extract a fused representation of the two types of brain network by projecting the structural network to the functional counterpart. Since the functional network is dynamic and the structural network is static, mapping a static object to a dynamic object is suboptimal. However, mapping in the opposite direction is not feasible due to the non-negativity requirement of current graph learning techniques. Here, we propose a novel graph learning framework, known as Deep Signed Brain Networks (DSBN), with a signed graph encoder that, from an opposite perspective, learns the cross-modality representations by projecting the functional network to the structural counterpart. We validate our framework on clinical phenotype and neurodegenerative disease prediction tasks using two independent, publicly available datasets (HCP and OASIS). The experimental results clearly demonstrate the advantages of our model compared to several state-of-the-art methods.

Bohao Yang, Kun Zhao, Dong Liu et al.

Automatic open-domain dialogue evaluation has attracted increasing attention, yet remains challenging due to the complexity of assessing response appropriateness. Traditional evaluation metrics, typically trained with true positive and randomly selected negative responses, tend to assign higher scores to responses that share greater content similarity with contexts. However, adversarial negative responses, despite possessing high lexical overlap with contexts, can be semantically incongruous. Consequently, existing metrics struggle to effectively evaluate such responses, resulting in low correlations with human judgments. While recent studies have demonstrated the effectiveness of Large Language Models (LLMs) for open-domain dialogue evaluation, they still face challenges in handling adversarial negative examples. We propose a novel evaluation framework that integrates Abstract Meaning Representation (AMR) enhanced domain-specific language models (SLMs) with LLMs. Our SLMs explicitly incorporate AMR graph information through a gating mechanism for enhanced semantic representation learning, while both SLM predictions and AMR knowledge are integrated into LLM prompts for robust evaluation. Extensive experiments on open-domain dialogue evaluation tasks demonstrate the superiority of our method compared to state-of-the-art baselines. Our comprehensive ablation studies reveal that AMR graph information contributes substantially more to performance improvements. Our framework achieves strong correlations with human judgments across multiple datasets, establishing a new benchmark for dialogue evaluation. Our code and data are publicly available.

Bao Hoang, Yijiang Pang, Siqi Liang et al.

Independent and identically distributed (i.i.d.) data is essential to many data analysis and modeling techniques. In the medical domain, collecting data from multiple sites or institutions is a common strategy that guarantees sufficient clinical diversity, determined by the decentralized nature of medical data. However, data from various sites are easily biased by the local environment or facilities, thereby violating the i.i.d. rule. A common strategy is to harmonize the site bias while retaining important biological information. The ComBat is among the most popular harmonization approaches and has recently been extended to handle distributed sites. However, when faced with situations involving newly joined sites in training or evaluating data from unknown/unseen sites, ComBat lacks compatibility and requires retraining with data from all the sites. The retraining leads to significant computational and logistic overhead that is usually prohibitive. In this work, we develop a novel Cluster ComBat harmonization algorithm, which leverages cluster patterns of the data in different sites and greatly advances the usability of ComBat harmonization. We use extensive simulation and real medical imaging data from ADNI to demonstrate the superiority of the proposed approach. Our codes are provided in https://github.com/illidanlab/distributed-cluster-harmonization.

Zhaoming Kong, Lichao Sun, Hao Peng et al.

In this paper, we propose MGNet, a simple and effective multiplex graph convolutional network (GCN) model for multimodal brain network analysis. The proposed method integrates tensor representation into the multiplex GCN model to extract the latent structures of a set of multimodal brain networks, which allows an intuitive 'grasping' of the common space for multimodal data. Multimodal representations are then generated with multiplex GCNs to capture specific graph structures. We conduct classification task on two challenging real-world datasets (HIV and Bipolar disorder), and the proposed MGNet demonstrates state-of-the-art performance compared to competitive benchmark methods. Apart from objective evaluations, this study may bear special significance upon network theory to the understanding of human connectome in different modalities. The code is available at https://github.com/ZhaomingKong/MGNets.

Kai Ye, Tiejin Chen, Hua Wei et al.

The Evidential Regression Network (ERN) represents a novel approach that integrates deep learning with Dempster-Shafer's theory to predict a target and quantify the associated uncertainty. Guided by the underlying theory, specific activation functions must be employed to enforce non-negative values, which is a constraint that compromises model performance by limiting its ability to learn from all samples. This paper provides a theoretical analysis of this limitation and introduces an improvement to overcome it. Initially, we define the region where the models can't effectively learn from the samples. Following this, we thoroughly analyze the ERN and investigate this constraint. Leveraging the insights from our analysis, we address the limitation by introducing a novel regularization term that empowers the ERN to learn from the whole training set. Our extensive experiments substantiate our theoretical findings and demonstrate the effectiveness of the proposed solution.

Kaiqiao Han, Yi Yang, Zijie Huang et al.

Brain network analysis is vital for understanding the neural interactions regarding brain structures and functions, and identifying potential biomarkers for clinical phenotypes. However, widely used brain signals such as Blood Oxygen Level Dependent (BOLD) time series generated from functional Magnetic Resonance Imaging (fMRI) often manifest three challenges: (1) missing values, (2) irregular samples, and (3) sampling misalignment, due to instrumental limitations, impacting downstream brain network analysis and clinical outcome predictions. In this work, we propose a novel model called BrainODE to achieve continuous modeling of dynamic brain signals using Ordinary Differential Equations (ODE). By learning latent initial values and neural ODE functions from irregular time series, BrainODE effectively reconstructs brain signals at any time point, mitigating the aforementioned three data challenges of brain signals altogether. Comprehensive experimental results on real-world neuroimaging datasets demonstrate the superior performance of BrainODE and its capability of addressing the three data challenges.

Haoteng Tang, Guodong Liu, Siyuan Dai et al.

The MRI-derived brain network serves as a pivotal instrument in elucidating both the structural and functional aspects of the brain, encompassing the ramifications of diseases and developmental processes. However, prevailing methodologies, often focusing on synchronous BOLD signals from functional MRI (fMRI), may not capture directional influences among brain regions and rarely tackle temporal functional dynamics. In this study, we first construct the brain-effective network via the dynamic causal model. Subsequently, we introduce an interpretable graph learning framework termed Spatio-Temporal Embedding ODE (STE-ODE). This framework incorporates specifically designed directed node embedding layers, aiming at capturing the dynamic interplay between structural and effective networks via an ordinary differential equation (ODE) model, which characterizes spatial-temporal brain dynamics. Our framework is validated on several clinical phenotype prediction tasks using two independent publicly available datasets (HCP and OASIS). The experimental results clearly demonstrate the advantages of our model compared to several state-of-the-art methods.

Feiyu Yin, Yu Lei, Siyuan Dai et al.

Brain connectivity alternations associated with brain disorders have been widely reported in resting-state functional imaging (rs-fMRI) and diffusion tensor imaging (DTI). While many dual-modal fusion methods based on graph neural networks (GNNs) have been proposed, they generally follow homogenous fusion ways ignoring rich heterogeneity of dual-modal information. To address this issue, we propose a novel method that integrates functional and structural connectivity based on heterogeneous graph neural networks (HGNNs) to better leverage the rich heterogeneity in dual-modal images. We firstly use blood oxygen level dependency and whiter matter structure information provided by rs-fMRI and DTI to establish homo-meta-path, capturing node relationships within the same modality. At the same time, we propose to establish hetero-meta-path based on structure-function coupling and brain community searching to capture relations among cross-modal nodes. Secondly, we further introduce a heterogeneous graph pooling strategy that automatically balances homo- and hetero-meta-path, effectively leveraging heterogeneous information and preventing feature confusion after pooling. Thirdly, based on the flexibility of heterogeneous graphs, we propose a heterogeneous graph data augmentation approach that can conveniently address the sample imbalance issue commonly seen in clinical diagnosis. We evaluate our method on ADNI-3 dataset for mild cognitive impairment (MCI) diagnosis. Experimental results indicate the proposed method is effective and superior to other algorithms, with a mean classification accuracy of 93.3%.

Kun Zhao, Bohao Yang, Chen Tang et al.

Large Language Models (LLMs) excel at many tasks but struggle with ambiguous scenarios where multiple valid responses exist, often yielding unreliable results. Conversely, Small Language Models (SLMs) demonstrate robustness in such scenarios but are susceptible to misleading or adversarial inputs. We observed that LLMs handle negative examples effectively, while SLMs excel with positive examples. To leverage their complementary strengths, we introduce SLIDE (Small and Large Integrated for Dialogue Evaluation), a method integrating SLMs and LLMs via adaptive weighting. Building on SLIDE, we further propose a Dual-Refinement Evaluation (DRE) method to enhance SLM-LLM integration: (1) SLM-generated insights guide the LLM to produce initial evaluations; (2) SLM-derived adjustments refine the LLM's scores for improved accuracy. Experiments demonstrate that DRE outperforms existing methods, showing stronger alignment with human judgment across diverse benchmarks. This work illustrates how combining small and large models can yield more reliable evaluation tools, particularly for open-ended tasks such as dialogue evaluation.

Reza Shirkavand, Liang Zhan, Heng Huang et al.

Recent advancements in the acquisition of various brain data sources have created new opportunities for integrating multimodal brain data to assist in early detection of complex brain disorders. However, current data integration approaches typically need a complete set of biomedical data modalities, which may not always be feasible, as some modalities are only available in large-scale research cohorts and are prohibitive to collect in routine clinical practice. Especially in studies of brain diseases, research cohorts may include both neuroimaging data and genetic data, but for practical clinical diagnosis, we often need to make disease predictions only based on neuroimages. As a result, it is desired to design machine learning models which can use all available data (different data could provide complementary information) during training but conduct inference using only the most common data modality. We propose a new incomplete multimodal data integration approach that employs transformers and generative adversarial networks to effectively exploit auxiliary modalities available during training in order to improve the performance of a unimodal model at inference. We apply our new method to predict cognitive degeneration and disease outcomes using the multimodal imaging genetic data from Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. Experimental results demonstrate that our approach outperforms the related machine learning and deep learning methods by a significant margin.

Haozhe Jia, Haoteng Tang, Guixiang Ma et al.

Automated and accurate segmentation of the infected regions in computed tomography (CT) images is critical for the prediction of the pathological stage and treatment response of COVID-19. Several deep convolutional neural networks (DCNNs) have been designed for this task, whose performance, however, tends to be suppressed by their limited local receptive fields and insufficient global reasoning ability. In this paper, we propose a pixel-wise sparse graph reasoning (PSGR) module and insert it into a segmentation network to enhance the modeling of long-range dependencies for COVID-19 infected region segmentation in CT images. In the PSGR module, a graph is first constructed by projecting each pixel on a node based on the features produced by the segmentation backbone, and then converted into a sparsely-connected graph by keeping only K strongest connections to each uncertain pixel. The long-range information reasoning is performed on the sparsely-connected graph to generate enhanced features. The advantages of this module are two-fold: (1) the pixel-wise mapping strategy not only avoids imprecise pixel-to-node projections but also preserves the inherent information of each pixel for global reasoning; and (2) the sparsely-connected graph construction results in effective information retrieval and reduction of the noise propagation. The proposed solution has been evaluated against four widely-used segmentation models on three public datasets. The results show that the segmentation model equipped with our PSGR module can effectively segment COVID-19 infected regions in CT images, outperforming all other competing models.

Haoteng Tang, Haozhe Jia, Weidong Cai et al.

In this paper, we propose a Boundary-aware Graph Reasoning (BGR) module to learn long-range contextual features for semantic segmentation. Rather than directly construct the graph based on the backbone features, our BGR module explores a reasonable way to combine segmentation erroneous regions with the graph construction scenario. Motivated by the fact that most hard-to-segment pixels broadly distribute on boundary regions, our BGR module uses the boundary score map as prior knowledge to intensify the graph node connections and thereby guide the graph reasoning focus on boundary regions. In addition, we employ an efficient graph convolution implementation to reduce the computational cost, which benefits the integration of our BGR module into current segmentation backbones. Extensive experiments on three challenging segmentation benchmarks demonstrate the effectiveness of our proposed BGR module for semantic segmentation.

Haoteng Tang, Guixiang Ma, Lifang He et al.

Recent years have witnessed the emergence and flourishing of hierarchical graph pooling neural networks (HGPNNs) which are effective graph representation learning approaches for graph level tasks such as graph classification. However, current HGPNNs do not take full advantage of the graph's intrinsic structures (e.g., community structure). Moreover, the pooling operations in existing HGPNNs are difficult to be interpreted. In this paper, we propose a new interpretable graph pooling framework - CommPOOL, that can capture and preserve the hierarchical community structure of graphs in the graph representation learning process. Specifically, the proposed community pooling mechanism in CommPOOL utilizes an unsupervised approach for capturing the inherent community structure of graphs in an interpretable manner. CommPOOL is a general and flexible framework for hierarchical graph representation learning that can further facilitate various graph-level tasks. Evaluations on five public benchmark datasets and one synthetic dataset demonstrate the superior performance of CommPOOL in graph representation learning for graph classification compared to the state-of-the-art baseline methods, and its effectiveness in capturing and preserving the community structure of graphs.

Wen Zhang, Liang Zhan, Paul Thompson et al.

Applying network science approaches to investigate the functions and anatomy of the human brain is prevalent in modern medical imaging analysis. Due to the complex network topology, for an individual brain, mining a discriminative network representation from the multimodal brain networks is non-trivial. The recent success of deep learning techniques on graph-structured data suggests a new way to model the non-linear cross-modality relationship. However, current deep brain network methods either ignore the intrinsic graph topology or require a network basis shared within a group. To address these challenges, we propose a novel end-to-end deep graph representation learning (Deep Multimodal Brain Networks - DMBN) to fuse multimodal brain networks. Specifically, we decipher the cross-modality relationship through a graph encoding and decoding process. The higher-order network mappings from brain structural networks to functional networks are learned in the node domain. The learned network representation is a set of node features that are informative to induce brain saliency maps in a supervised manner. We test our framework in both synthetic and real image data. The experimental results show the superiority of the proposed method over some other state-of-the-art deep brain network models.

Haoteng Tang, Guixiang Ma, Yurong Chen et al.

Recent years have witnessed the emergence and development of graph neural networks (GNNs), which have been shown as a powerful approach for graph representation learning in many tasks, such as node classification and graph classification. The research on the robustness of these models has also started to attract attentions in the machine learning field. However, most of the existing work in this area focus on the GNNs for node-level tasks, while little work has been done to study the robustness of the GNNs for the graph classification task. In this paper, we aim to explore the vulnerability of the Hierarchical Graph Pooling (HGP) Neural Networks, which are advanced GNNs that perform very well in the graph classification in terms of prediction accuracy. We propose an adversarial attack framework for this task. Specifically, we design a surrogate model that consists of convolutional and pooling operators to generate adversarial samples to fool the hierarchical GNN-based graph classification models. We set the preserved nodes by the pooling operator as our attack targets, and then we perturb the attack targets slightly to fool the pooling operator in hierarchical GNNs so that they will select the wrong nodes to preserve. We show the adversarial samples generated from multiple datasets by our surrogate model have enough transferability to attack current state-of-art graph classification models. Furthermore, we conduct the robust train on the target models and demonstrate that the retrained graph classification models are able to better defend against the attack from the adversarial samples. To the best of our knowledge, this is the first work on the adversarial attack against hierarchical GNN-based graph classification models.

Mengying Sun, Inci M. Baytas, Liang Zhan et al.

Over the past decade a wide spectrum of machine learning models have been developed to model the neurodegenerative diseases, associating biomarkers, especially non-intrusive neuroimaging markers, with key clinical scores measuring the cognitive status of patients. Multi-task learning (MTL) has been commonly utilized by these studies to address high dimensionality and small cohort size challenges. However, most existing MTL approaches are based on linear models and suffer from two major limitations: 1) they cannot explicitly consider upper/lower bounds in these clinical scores; 2) they lack the capability to capture complicated non-linear interactions among the variables. In this paper, we propose Subspace Network, an efficient deep modeling approach for non-linear multi-task censored regression. Each layer of the subspace network performs a multi-task censored regression to improve upon the predictions from the last layer via sketching a low-dimensional subspace to perform knowledge transfer among learning tasks. Under mild assumptions, for each layer the parametric subspace can be recovered using only one pass of training data. Empirical results demonstrate that the proposed subspace network quickly picks up the correct parameter subspaces, and outperforms state-of-the-arts in predicting neurodegenerative clinical scores using information in brain imaging.

Johnson J. G. Keiriz, Liang Zhan, Morris Chukhman et al.

Visually comparing brain networks, or connectomes, is an essential task in the field of neuroscience. Especially relevant to the field of clinical neuroscience, group studies that examine differences between populations or changes over time within a population enable neuroscientists to reason about effective diagnoses and treatments for a range of neuropsychiatric disorders. In this paper, we specifically explore how visual analytics tools can be used to facilitate various clinical neuroscience tasks, in which observation and analysis of meaningful patterns in the connectome can support patient diagnosis and treatment. We conduct a survey of visualization tasks that enable clinical neuroscience activities, and further explore how existing connectome visualization tools support or fail to support these tasks. Based on our investigation of these tasks, we introduce a novel visualization tool, NeuroCave, to support group studies analyses. We discuss how our design decisions (the use of immersive visualization, the use of hierarchical clustering and dimensionality reduction techniques, and the choice of visual encodings) are motivated by these tasks. We evaluate NeuroCave through two use cases that illustrate the utility of interactive connectome visualization in clinical neuroscience contexts. In the first use case, we study sex differences using functional connectomes and discover hidden connectome patterns associated with well-known cognitive differences in spatial and verbal abilities. In the second use case, we show how the utility of visualizing the brain in different topological space coupled with clustering information can reveal the brain's intrinsic structure.

Qingyang Li, Tao Yang, Liang Zhan et al.

Genome-wide association studies (GWAS) offer new opportunities to identify genetic risk factors for Alzheimer's disease (AD). Recently, collaborative efforts across different institutions emerged that enhance the power of many existing techniques on individual institution data. However, a major barrier to collaborative studies of GWAS is that many institutions need to preserve individual data privacy. To address this challenge, we propose a novel distributed framework, termed Local Query Model (LQM) to detect risk SNPs for AD across multiple research institutions. To accelerate the learning process, we propose a Distributed Enhanced Dual Polytope Projection (D-EDPP) screening rule to identify irrelevant features and remove them from the optimization. To the best of our knowledge, this is the first successful run of the computationally intensive model selection procedure to learn a consistent model across different institutions without compromising their privacy while ranking the SNPs that may collectively affect AD. Empirical studies are conducted on 809 subjects with 5.9 million SNP features which are distributed across three individual institutions. D-EDPP achieved a 66-fold speed-up by effectively identifying irrelevant features.